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Improved quality of life (QoL) is an important outcome goal following epilepsy surgery. This study aims to quantify change in QoL for adults with drug‐resistant epilepsy (DRE) who undergo epilepsy surgery, and to explore clinicodemographic factors associated with these changes. We conducted a systematic review and meta‐analysis using Medline, Embase, and Cochrane Central Register of Controlled Trials. All studies reporting pre‐ and post‐epilepsy surgery QoL scores in adults with DRE via validated instruments were included. Meta‐analysis assessed the postsurgery change in QoL. Meta‐regression assessed the effect of postoperative seizure outcomes on postoperative QoL as well as change in pre‐ and postoperative QoL scores. A total of 3774 titles and abstracts were reviewed, and ultimately 16 studies, comprising 1182 unique patients, were included. Quality of Life in Epilepsy Inventory–31 item (QOLIE‐31) meta‐analysis included six studies, and QOLIE‐89 meta‐analysis included four studies. Postoperative change in raw score was 20.5 for QOLIE‐31 (95% confidence interval [CI] = 10.9–30.1, I2 = 95.5) and 12.1 for QOLIE‐89 (95% CI = 8.0–16.1, I2 = 55.0%). This corresponds to clinically meaningful QOL improvements. Meta‐regression demonstrated a higher postoperative QOLIE‐31 score as well as change in pre‐ and postoperative QOLIE‐31 score among studies of cohorts with higher proportions of patients with favorable seizure outcomes. At an individual study level, preoperative absence of mood disorders, better preoperative cognition, fewer trials of antiseizure medications before surgery, high levels of conscientiousness and openness to experience at the baseline, engagement in paid employment before and after surgery, and not being on antidepressants following surgery were associated with improved postoperative QoL. This study demonstrates the potential for epilepsy surgery to provide clinically meaningful improvements in QoL, as well as identifies clinicodemographic factors associated with this outcome. Limitations include substantial heterogeneity between individual studies and high risk of bias. [ABSTRACT FROM AUTHOR]

Objective: New‐onset seizures affect up to 10% of people over their lifetime, however, their health economic impact has not been well‐studied. This prospective multicenter study will collect patient‐reported outcome measures (PROMs) from adults with new‐onset seizures seen in six Seizure Clinics across Melbourne, Australia and The University of Colorado, USA. Methods: Approximately 450 eligible patients will be enrolled in the study at or following their initial attendance to Seizure Clinics at the study hospitals. Inclusion criteria for the study group are those with new‐onset acute symptomatic seizures, new‐onset unprovoked seizures, and new‐onset epilepsy. Inclusion criteria for the three comparator groups are those with noncardiac syncope, those with psychogenic nonepileptic seizures, as well as published PROMs data from the Australian general population. Exclusion criteria are those aged less than 18 years, those with a preexisting epilepsy diagnosis, and those with intellectual disabilities or other impairments which would preclude them from comprehending and completing the questionnaires. Patients will complete eight online questionnaires regarding the effect that their seizures (or seizure mimics) have had on various aspects of their life. These questionnaires will be readministered at 6 and 12 months. Patients with new‐diagnosis epilepsy will also be asked to share the reasons why they have accepted or declined antiseizure medications. Analysis: Primary outcome measures will be quality of life, work productivity, informal care needs, and mood, at baseline compared to 6 and 12 months later for those with new‐onset seizures and comparing these outcomes to those in the three comparator groups. Secondary outcomes include mapping of QoLIE‐31 to the EQ‐5D‐5L in epilepsy, modelling indirect costs of new‐onset seizures, and exploring why patients may or may not wish to take antiseizure medications. Significance: These data will form an evidence‐base for future studies that examine the effectiveness of various healthcare interventions for new‐onset seizure patients. Ethics and dissemination: This study is approved by the Alfred Health Human Research Ethics Committee (SERP: 52 538, Alfred HREC: 307/19), the Austin Health Human Research Ethics Committee (HREC/59148/Austin‐2019), and the Colorado Multiple Institutional Review Board (COMIRB) (COMIRB #20‐3028). ANZCTR trial registration number: ACTRN12621000908831. [ABSTRACT FROM AUTHOR]

Disorders of consciousness (DoC) are states of impaired arousal or awareness. Deep brain stimulation (DBS) is a potential treatment, but outcomes vary, possibly due to differences in patient characteristics, electrode placement, or stimulation of specific brain networks. We studied 40 patients with DoC who underwent DBS targeting the thalamic centromedian-parafascicular complex. Better-preserved gray matter, especially in the striatum, correlated with consciousness improvement. Stimulation was most effective when electric fields extended into parafascicular and subparafascicular nuclei-ventral to the centromedian nucleus, near the midbrain-and when it engaged projection pathways of the ascending arousal network, including the hypothalamus, brainstem, and frontal lobe. Moreover, effective DBS sites were connected to networks similar to those underlying impaired consciousness due to generalized absence seizures and acquired lesions. These findings support the therapeutic potential of DBS for DoC, emphasizing the importance of precise targeting and revealing a broader link between effective DoC treatment and mechanisms underlying other conscciousness-impairing conditions., Competing Interests: COMPETING INTERESTS AELW, MR, HF, FLWVJS, JT, SBS, JL, MMJC, KB, MUF, RJ, JEI, PWC, DF, ADB, BLE, and DC have no competing interests to report. MDF has intellectual property on the use of brain connectivity imaging to analyze lesions and guide brain stimulation, has consulted for Magnus Medical, Soterix, Abbott, Boston Scientific, and Tal Medical, and has received research funding from Neuronetics. AH reports lecture fees for Boston Scientific and is a consultant for Neuromodulation and Abbott. JDR has received past consulting payments from Medtronic, Corlieve, ClearPoint, Medtronic, and NeuroPace, and currently consults for Turing Medical.

Objective: The MAST family of microtubule-associated serine-threonine kinases (STKs) have distinct expression patterns in the developing and mature human and mouse brain. To date, only MAST1 has been conclusively associated with neurological disease, with de novo variants in individuals with a neurodevelopmental disorder, including a mega corpus callosum., Methods: Using exome sequencing, we identify MAST3 missense variants in individuals with epilepsy. We also assess the effect of these variants on the ability of MAST3 to phosphorylate the target gene product ARPP-16 in HEK293T cells., Results: We identify de novo missense variants in the STK domain in 11 individuals, including 2 recurrent variants p.G510S (n = 5) and p.G515S (n = 3). All 11 individuals had developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at <2 years of age. All patients developed multiple seizure types, 9 of 11 patients had seizures triggered by fever and 9 of 11 patients had drug-resistant seizures. In vitro analysis of HEK293T cells transfected with MAST3 cDNA carrying a subset of these patient-specific missense variants demonstrated variable but generally lower expression, with concomitant increased phosphorylation of the MAST3 target, ARPP-16, compared to wild-type. These findings suggest the patient-specific variants may confer MAST3 gain-of-function. Moreover, single-nuclei RNA sequencing and immunohistochemistry shows that MAST3 expression is restricted to excitatory neurons in the cortex late in prenatal development and postnatally., Interpretation: In summary, we describe MAST3 as a novel epilepsy-associated gene with a potential gain-of-function pathogenic mechanism that may be primarily restricted to excitatory neurons in the cortex. ANN NEUROL 2021;90:274-284., (© 2021 American Neurological Association.)